ClinVar Miner

Submissions for variant NM_025216.3(WNT10A):c.637G>A (p.Gly213Ser)

gnomAD frequency: 0.00071  dbSNP: rs147680216
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000490390 SCV000267562 uncertain significance Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 2016-03-18 criteria provided, single submitter reference population
Illumina Laboratory Services, Illumina RCV000128463 SCV000427556 likely benign Tooth agenesis, selective, 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000270809 SCV000427557 benign SchC6pf-Schulz-Passarge syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000325824 SCV000427558 benign Odonto-onycho-dermal dysplasia 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000490390 SCV001013761 benign Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 2025-01-09 criteria provided, single submitter clinical testing
GeneDx RCV001555273 SCV001776659 likely pathogenic not provided 2024-07-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34878701, 33932139, 31103801, 28944914, 31180159, 24312213, 30555066, 24449199, 29367877, 23401279, 24311251, 27657131, 29178643, 25629078, 34426522, 33034246, 24458874, 35537890, LiuH[article]2022, 36071541, 34834569, 34184264, 35546689, 33329022, 24043634, 36143186, 37228816, 37005710, 38163170, 36832485, 38280992)
Stomatology Center, Xiangya Hospital, Central South University RCV003233110 SCV003930329 pathogenic Tooth agenesis, selective, 2 criteria provided, single submitter research We used whole exome sequencing to compare tooth loss gene loci between two brothers with hypophidrotic ectodermal dysplasia (HED), analyze the difference of tooth loss phenotype, and explore its mechanism. wes showed that an EDA mutation was found in both older and younger brothers (c.878T>G), and the compound heterozygous mutation of WNT10A (c.511C>T and c.637G>A) Found only in the elder brothers. Prediction of secondary and tertiary structures of the WNT10A variants (p. R171C, p.G213S) indicated the impaired function of the molecule. The elder brothers have a more severe tooth loss phenotype than younger brothers. It has been reported that eda c.878T>G mutation caused HED (PMID: 30526585). We believe that EDA is the main pathogenic gene in the two patients, and the compound heterozygous WNT10A missense mutation can aggravate the HED phenotype caused by EDA mutation, resulting in a severe edentulous mandible phenotype in the elder brother.
OMIM RCV000128463 SCV000172165 pathogenic Tooth agenesis, selective, 4 2014-02-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics, Yale University RCV000845115 SCV000987051 uncertain significance Tooth agenesis 2014-09-15 no assertion criteria provided literature only
Department of Second Dental Center, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine RCV000128463 SCV004023333 uncertain significance Tooth agenesis, selective, 4 no assertion criteria provided clinical testing
Department of Second Dental Center, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine RCV000325824 SCV004032521 uncertain significance Odonto-onycho-dermal dysplasia no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004734670 SCV005358819 likely pathogenic WNT10A-related disorder 2024-03-19 no assertion criteria provided clinical testing The WNT10A c.637G>A variant is predicted to result in the amino acid substitution p.Gly213Ser. This variant has been reported in the compound heterozygous state, with another variant in WNT10A (phase unknown), with variants in the EDA gene (phase unknown), and in the heterozygous state in individuals with mild ectodermal dysplasia or tooth agenesis (Patient 14, Plaisancié et al. 2013. PubMed ID: 23401279; Proband 52 and 53, He et al. 2013. PubMed ID: 2431221; Song et al. 2013. PubMed ID: 24043634; Family 1, Kantaputra et al. 2014. PubMed ID: 24311251; Yang et al. 2014. PubMed ID: 25629078; Yuan et al. 2017. PubMed ID: 29178643; Park et al. 2019. PubMed ID: 31103801). Of note, this variant has been reported in patients and in normal control populations (Song et al. 2013. PubMed ID: 24043634). Protein structure analysis predicted that this variant would alter protein structure (He et al. 2013. PubMed ID: 24312213). This variant is reported in 2.8% of alleles in individuals of East Asian descent in gnomAD including 14 homozygous individuals. This variant has conflicting interpretations in ClinVar ranging from likely pathogenic to uncertain significance to likely benign to benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/139576/). Taken together, we classify this variant as likely pathogenic.

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